title: Varenicline, a partial agonist at neuronal nicotinic acetylcholine receptors, reduces nicotine-induced increases in 20% ethanol operant self-administration in Sprague-Dawley rats.
abstract: Alcohol and nicotine use disorders are often treated as separate diseases, despite evidence that approximately 80-90% of alcohol dependent individuals are also heavy smokers. Both nicotine and ethanol have been shown to interact with neuronal nicotinic acetylcholine receptors (nAChRs), suggesting these receptors are a common biological target for the effects of nicotine and ethanol in the brain. There are few studies that have examined the effects of co-administered nicotine and ethanol on the activity of nAChRs in rodents. In the present study, we show that Sprague-Dawley rats, a strain often used for nicotine studies but not as often for voluntary ethanol intake studies, will consume 20% ethanol using both the intermittent-access two-bottle-choice and operant self-administration models without the need for sucrose fading. We show that nicotine (0.2 mg/kg and 0.8 mg/kg, s.c.) significantly increases operant 20% ethanol self-administration and varenicline (2 mg/kg, s.c), a partial agonist at nAChRs, significantly decreases operant ethanol self-administration and nicotine-induced increases in ethanol self-administration. This suggests that nAChRs play an important role in increasing ethanol self-administration and that varenicline may be an efficacious treatment for alcohol and nicotine co-dependencies.
authors.affiliation: Ernest Gallo Clinic and Research Center at the University of California-San Francisco, 5858 Horton Street, Emeryville, CA 94608, USA.
authors.forename: Jade J
authors.initials: JJ
authors.lastname: Bito-Onon
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Simms
authors.forename: Susmita
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Joan
authors.initials: J
authors.lastname: Holgate
authors.forename: Selena E
authors.initials: SE
authors.lastname: Bartlett
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012646:Self Administration; D013268:Stimulation, Chemical; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D011978:Receptors, Nicotinic; D009538:Nicotine; D000068580:Varenicline